title: Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer.
abstract: Recently, a subset of IL-17 producing T cells distinct from Th1 or Th2 cells has been described as key players in inflammation and autoimmune diseases as well as cancer development. In this study, we investigated the expression level of IL-17 and T helper 17 (Th17)-related cytokines in gastric cancer tissues and assessed the association of their expression with angiogenesis and their clinicopathological parameters. Tumor and adjacent normal tissues were obtained from 82 patients with gastric cancer. IL-17, IL-21 and IL-23 mRNA expression levels were quantified by real-time RT-PCR. Th17 infiltration, microvessel density and neutrophil infiltration in tumor tissues were examined by immunohistochemistry and double immunofluorescence histochemistry. Expression of IL-17, IL-21 and IL-23 mRNA was found to be significantly up-regulated in tumor tissues compared with adjacent normal tissues. The expression level of IL-17 mRNA strongly and positively correlated with that of IL-21 mRNA in tumor tissue. The number of vascular endothelial cells and infiltrating neutrophils was significantly larger in tumors expressing a high level of IL-17 mRNA than in tumors expressing a low level of IL-17 mRNA. In tumor tissues most CD4+ cells were stained with anti-IL-17 antibody. The expression level of IL-17 mRNA in gastric tumors was associated with the depth of the tumors, lymph-vascular invasion and lymph node involvement, suggesting that IL-17 obviously was related to tumor progression. IL-17 and IL-21, which regulates IL-17, would be potential therapeutic targets for the treatment of gastric cancer.
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iida
authors.forename: Makoto
authors.initials: M
authors.lastname: Iwahashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Katsuda
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ishida
authors.forename: Mikihito
authors.initials: M
authors.lastname: Nakamori
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Teiji
authors.initials: T
authors.lastname: Naka
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Ojima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ueda
authors.forename: Keiji
authors.initials: K
authors.lastname: Hayata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes; D018450:Disease Progression; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics; D007378:Interleukins / Q000235:genetics; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D000098546:Interleukin-21